Lactam compounds and pharmaceutical use thereof

1. A compound of formula (I) or a pharmaceutically acceptable salt thereof:

wherein A represents an aromatic ring, a heterocyclic ring or an aliphatic ring; R 2 , R 3 and R 4 may be the same or different from one another and independently represent a hydrogen atom, a halogen atom, a hydroxyl group, an alkyl group, a mercapto group, an alkoxyl group, an alkylthio group, an alkylsulfonyl group, an acyl group, an acyloxyl group, an amino group, an alkylamino group, a carboxyl group, an alkoxycarbonyl group, a carbamoyl group, a nitro group, a cyano group, a trifluoromethyl group, an alkenyl group which may have a substituent(s), an alkynyl group which may have a substituent(s), an aryl group which may have a substituent(s), a heteroaryl group which may have a substituent(s), a benzyloxyl group which may have a substituent(s), an aryloxyl group which may have a substituent(s), a heteroaryloxyl group which may have a substituent(s), an arylamino group which may have a substituent(s), an arylvinyl group which may have a substituent(s) or an arylethynyl group which may have a substituent(s); B represents a fused cyclohexane ring which may have a substituent(s); —X— and —Y— may be the same or different from one another and they independently represent —NH— and —NR 5 —, wherein R 5 represents a lower alkyl group which may have a substituent(s), an acyl group which may have a substituent(s), an alkoxycarbonyl group which may have a substituent(s), a carbamoyl group which may have a substituent(s) or a sulfonyl group which may have a substituent(s); —Z— represents —CH 2 — or —CR 6 R 7 —, wherein R 6 and R 7 may be the same or different from each other and they independently represent a hydrogen atom, a halogen atom, a hydroxyl group, an alkyl group which may have a substituent(s), an aryl group, a mercapto group, an alkoxyl group, an alkylthio group, an alkylsulfonyl group, an acyl group, an acyloxyl group, an amino group, an alkylamino group, a carboxyl group, an alkoxycarbonyl group, a carbamoyl group, a nitro group, a cyano group or a trifluoromethyl group; —W— represents —NR 1 —, wherein R 1 represents a hydrogen atom, a lower alkyl group which may have a substituent(s) or an aryl group which may have a substituent(s); and a, b and c each represent the position of carbon atom;

said heterocyclic ring is selected from the group consisting of pyridine ring, dihydropyran ring, pyridazine ring, pyrimidine ring, pyrazine ring, pyrrole ring, furan ring, thiophene ring, oxazole ring, isoxazole ring, pyrazole ring, imidazole ring, thiazole ring, isothiazole ring, thiadiazole ring, pyrrolidine ring, piperidine ring, piperazine ring, indole ring, isoindole ring, benzofuran ring, isobenzofuran ring, benzothiophene ring, benzopyrazole ring, benzoimidazole ring, benzoxazole ring, benzothiazole ring, purine ring, pyrazolopyridine ring, quinoline ring, isoquinoline ring, naphthyridine ring, quinazoline ring, benzodiazepine ring, carbazole ring, and dibenzofuran ring;

said acyl group is selected from the group consisting of formyl group, acetyl group, propionyl group, butyryl group, isobutyryl group, valeryl group, isovaleryl group, pivaloyl group, hexanoyl group, acryloyl group, methacryloyl group, crotonoyl group, isocrotonoyl group, benzoyl group, naphthoyl group, furanyl carbonyl group, thienyl carbonyl group, isoxazolyl carbonyl group, and thiazolyl carbonyl group;

said acyloxyl group is selected from the group consisting of formyloxyl group, acetyloxy group, propionyloxyl group, butyryloxyl group, isobutyryloxyl group, valeryloxyl group, isovaleryloxyl group, pivaloyloxyl group, hexanoyloxyl group, acryloyloxyl group, methacryloyloxyl group, crotonoyloxyl group, isocrotonoyloxyl group, benzoyloxyl group, and naphthoyloxyl group;

said heteroaryl group is selected from the group consisting of pyridyl group, pyridazinyl group, pyrimidinyl group, pyrazinyl group, pyrrolyl group, furanyl group, thienyl group, oxazolyl group, isoxazolyl group, pyrazolyl group, imidazolyl group, thiazolyl group, isothiazolyl group, thiadiazolyl group, indolyl group, isoindolyl group, benzofuryl group, isobenzofuryl group, benzothienyl group, benzopyrazolyl group, benzoimidazolyl group, benzoxazolyl group, benzothiazolyl group, quinolyl group, isoquinolyl group, naphthylidinyl group, quinazolyl group, oxadiazolyl group, and pyridonyl group,

and wherein

the substituent(s) is selected from the group consisting of halogen atoms, hydroxyl group, alkyl groups, mercapto group, alkoxyl groups, alkylthio groups, alkylsulfonyl groups, acyl groups, acyloxyl groups, amino group, alkylamino groups, carboxyl group, alkoxycarbonyl groups, carbamoyl groups, nitro group, cyano group, trifluoromethyl group, aryl groups and heteroaryl groups.

2. The compound or pharmaceutically acceptable salt thereof according to claim 1 , wherein in general formula (I), R 2 , R 3 and R 4 may be the same or different from one another and independently represent a hydrogen atom, a halogen atom, a hydroxyl group, an alkyl group, a mercapto group, an alkoxyl group, an alkylthio group, an alkylsulfonyl group, an acyl group, an acyloxyl group, an amino group, an alkylamino group, a carboxyl group, an alkoxycarbonyl group, a carbamoyl group, a nitro group, a cyano group, a trifluoromethyl group, an aryl group which may have a substituent(s), a heteroaryl group which may have a substituent(s), a benzyloxyl group which may have a substituent(s), an aryloxyl group which may have a substituent(s), a heteroaryloxyl group which may have a substituent(s), an arylamino group which may have a substituent(s), an arylvinyl group which may have a substituent(s) or an arylethynyl group which may have a substituent(s); —X— and —Y— may be the same or different from one another and they independently represent —NH— or —NR 5 —, wherein R 5 represents a lower alkyl group or an acyl group which may have a substituent(s); —Z— represents —CH 2 — or —CR 6 R 7 —, wherein R 6 and R 7 may be the same or different from each other and they independently represent a hydrogen atom, a halogen atom, a hydroxyl group, an alkyl group, an aryl group, a mercapto group, an alkoxyl group, an alkylthio group, an alkylsulfonyl group, an acyl group, an acyloxyl group, an amino group, an alkylamino group, a carboxyl group, an alkoxycarbonyl group, a carbamoyl group, a nitro group, a cyano group or a trifluoromethyl group; and wherein:

(i) the substituent(s) is selected from the group consisting of halogen atoms, hydroxyl group, alkyl groups, aryl groups, mercapto group, alkoxyl groups, alkylthio groups, alkylsulfonyl groups, acyl groups, acyloxyl groups, amino group, alkylamino groups, carboxyl group, alkoxycarbonyl groups, carbamoyl groups, nitro group, cyano group and trifluoromethyl group.

3. The compound or pharmaceutically acceptable salt thereof according to claim 1 , wherein in general formula (I), —Z— represents —CH 2 — or —CR 6 R 7 — wherein R 6 and R 7 may be the same or different from each other and they independently represent a hydrogen atom, a halogen atom, a hydroxyl group, an alkyl group, a mercapto group, an alkoxyl group, an alkylthio group, an alkylsulfonyl group, an acyl group, an acyloxyl group, an amino group, an alkylamino group, a carboxyl group, an alkoxycarbonyl group, a carbamoyl group, a nitro group, a cyano group or a trifluoromethyl group.

4. The compound or pharmaceutically acceptable salt thereof according to claim 3 , wherein —Y— is —NR 5 —, wherein R 5 represents an acyl group having 1 to 7 carbon atoms which may have a substituent selected from the group consisting of halogen atoms, lower alkyloxy groups, hydroxy group, furyl group, thienyl group, oxazolyl group, isoxazolyl group, thiazolyl group, pyridyl group, pyrimidyl group and imidazolyl group.

5. The compound or pharmaceutically acceptable salt thereof according to claim 3 , wherein in general formula (I), A represents a benzene ring.

6. The compound or a pharmaceutically acceptable salt thereof according to claim 5 , wherein the absolute configuration of carbon atoms at a, b and c in general formula (I) is R or S independently from each other.

7. The compound or pharmaceutically acceptable salt thereof according to claim 6 , wherein the absolute configuration of carbon atoms at both a and b in general formula (I) is R and the absolute configuration of carbon atom at c is R or S.

8. The compound or pharmaceutically acceptable salt thereof according to claim 6 , wherein the absolute configuration of carbon atoms at both a and b in general formula (I) is S and the absolute configuration of carbon atoms in c is R or S.

9. A method for treating hypoglycemia, comprising administering to a subject in need thereof an effective amount of a compound or pharmaceutically acceptable salt thereof according to claim 1 .

10. A method for treating diabetes, diabetic peripheral neuropathy, diabetic nephropathy, diabetic retinopathy, diabetic macroangiopathy, impaired glucose tolerance or adiposis, which comprises administering to a subject in need thereof an effective amount of a compound or pharmaceutically acceptable salt thereof according to claim 1 .

11. A pharmaceutical composition comprising a compound or pharmaceutically acceptable salt thereof according to claim 1 and a pharmaceutically acceptable carrier.

12. A pharmaceutical composition comprising a compound or pharmaceutically acceptable salt thereof according to claim 2 and a pharmaceutically acceptable carrier.

13. A pharmaceutical composition comprising a compound or pharmaceutically acceptable salt thereof according to claim 3 and a pharmaceutically acceptable carrier.

14. A pharmaceutical composition comprising a compound or pharmaceutically acceptable salt thereof according to claim 4 and a pharmaceutically acceptable carrier.

15. A pharmaceutical composition comprising a compound or pharmaceutically acceptable salt thereof according to claim 5 and a pharmaceutically acceptable carrier.

16. A pharmaceutical composition comprising a compound or pharmaceutically acceptable salt thereof according to claim 6 and a pharmaceutically acceptable carrier.

17. A pharmaceutical composition comprising a compound or pharmaceutically acceptable salt thereof according to claim 7 and a pharmaceutically acceptable carrier.

18. A pharmaceutical composition comprising a compound or pharmaceutically acceptable salt thereof according to claim 8 and a pharmaceutically acceptable carrier.

19. A method for treating hypoglycemia, comprising administering to a subject in need thereof an effective amount of a compound or pharmaceutically acceptable salt thereof according to claim 2 .

20. A method for treating hypoglycemia, comprising administering to a subject in need thereof an effective amount of a compound or pharmaceutically acceptable salt thereof according to claim 3 .

21. A method for treating hypoglycemia, comprising administering to a subject in need thereof an effective amount of a compound or pharmaceutically acceptable salt thereof according to claim 4 .

22. A method for treating hypoglycemia, comprising administering to a subject in need thereof an effective amount of a compound or pharmaceutically acceptable salt thereof according to claim 5 .

23. A method for treating hypoglycemia, comprising administering to a subject in need thereof an effective amount of a compound or pharmaceutically acceptable salt thereof according to claim 6 .

24. A method for treating hypoglycemia, comprising administering to a subject in need thereof an effective amount of a compound or pharmaceutically acceptable salt thereof according to claim 7 .

25. A method for treating hypoglycemia, comprising administering to a subject in need thereof an effective amount of a compound or pharmaceutically acceptable salt thereof according to claim 8 .

26. A method for treating diabetes, diabetic peripheral neuropathy, diabetic nephropathy, diabetic retinopathy, diabetic macroangiopathy, impaired glucose tolerance or adiposis, which comprises administering to a subject in need thereof an effective amount of a compound or pharmaceutically acceptable salt thereof according to claim 2 .

27. A method for treating diabetes, diabetic peripheral neuropathy, diabetic nephropathy, diabetic retinopathy, diabetic macroangiopathy, impaired glucose tolerance or adiposis, which comprises administering to a subject in need thereof an effective amount of a compound or pharmaceutically acceptable salt thereof according to claim 3 .

28. A method for treating diabetes, diabetic peripheral neuropathy, diabetic nephropathy, diabetic retinopathy, diabetic macroangiopathy, impaired glucose tolerance or adiposis, which comprises administering to a subject in need thereof an effective amount of a compound or pharmaceutically acceptable salt thereof according to claim 4 .

29. A method for treating diabetes, diabetic peripheral neuropathy, diabetic nephropathy, diabetic retinopathy, diabetic macroangiopathy, impaired glucose tolerance or adiposis, which comprises administering to a subject in need thereof an effective amount of a compound or pharmaceutically acceptable salt thereof according to claim 5 .

30. A method for treating diabetes, diabetic peripheral neuropathy, diabetic nephropathy, diabetic retinopathy, diabetic macroangiopathy, impaired glucose tolerance or adiposis, which comprises administering to a subject in need thereof an effective amount of a compound or pharmaceutically acceptable salt thereof according to claim 6 .

31. A method for treating diabetes, diabetic peripheral neuropathy, diabetic nephropathy, diabetic retinopathy, diabetic macroangiopathy, impaired glucose tolerance or adiposis, which comprises administering to a subject in need thereof an effective amount of a compound or pharmaceutically acceptable salt thereof according to claim 7 .

32. A method for treating diabetes, diabetic peripheral neuropathy, diabetic nephropathy, diabetic retinopathy, diabetic macroangiopathy, impaired glucose tolerance or adiposis, which comprises administering to a subject in need thereof an effective amount of a compound or pharmaceutically acceptable salt thereof according to claim 8 .

33. The compound or pharmaceutically acceptable salt according to claim 1 , which has the structure:

wherein R is 2-OMe and R′ is COCH 2 OH.

34. The compound or pharmaceutically acceptable salt according to claim 1 , which has the structure:

wherein R is 2-Et and R′ is COCH 2 OEt.

35. The compound or pharmaceutically acceptable salt according to claim 1 , which has the structure:

wherein R is 2-Et and R′ is COCH 3 .

36. The compound or pharmaceutically acceptable salt according to claim 1 , which has the structure:

wherein R is H and R′ is COCH 2 CH 3 .

37. The compound or pharmaceutically acceptable salt according to claim 1 , which has the structure:

wherein R is H and R′ is COCH 2 OEt.

38. The compound or pharmaceutically acceptable salt according to claim 1 , which has the structure:

wherein R is 2-SMe and R′ is COCH 2 OH.

39. The compound or pharmaceutically acceptable salt according to claim 1 , which has the structure:

wherein R is H and R′ is COCH 2 OH.

40. A compound, of the formula:

wherein R is 2-OCF 3 and R′ is 3-(thiazol-2-yl)propanoyl or a pharmaceutically acceptable salt thereof.

41. A compound, of the formula:

wherein R1 is 2-OCF 3 , R2 is COCH 2 OH, R3 is H, and R4 is H or a pharmaceutically acceptable salt thereof.

42. The compound or pharmaceutically acceptable salt according to claim 1 , which has the structure:

wherein R1 is 2-SMe, R2 is COCH 3 , R3 is H, and R4 is H.

43. The compound or pharmaceutically acceptable salt according to claim 1 , which has the structure:

wherein R1 is 2-cyclopropyl, R2 is COCH 2 OH, R3 is H, and R4 is H.